RATIONALE: Drugs used in chemotherapy, such as gemcitabine and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine together with bevacizumab works in treating patients with metastatic breast cancer.
OBJECTIVES: Primary * To determine the 6-month progression-free survival rate of patients with metastatic breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and bevacizumab. Secondary * To determine the overall survival of patients treated with this regimen. * To determine the progression-free survival of patients treated with this regimen. * To determine the confirmed response rate in patients treated with this regimen. * To determine the duration of response in patients treated with this regimen. * To determine the time to treatment failure in patients treated with this regimen. * To determine the quality of life of patients treated with this regimen. OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and after every other course, and then after completion of treatment. After completion of study treatment, patients are followed periodically for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States
Reid Hospital & Health Care Services
Richmond, Indiana, United States
6-month Progression-free Survival (PFS) Rate
The primary endpoint of this trial is the 6-month progression-free survival rate. A patient is considered to be a 6-month progression-free survivor if the patient is 6 months from registration without a documentation of disease progression (note, the patient need not be on study treatment at 6 months to be considered a success). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.
Time frame: at 6 months
Overall Survival Time
Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).
Time frame: Up to 5 years
PFS Time
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. The distribution of time to progression will be estimated using the method of Kaplan-Meier (1958). Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.
Time frame: Up to 5 years
Confirmed Response (Complete or Partial Response) Rate
A confirmed response is defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The confirmed response rate (percentage) will be estimated by the number of confirmed responses in evaluable patients divided by the total number of evaluable patients multiplied by 100. The appropriate confidence interval will be calculated based on the binomial distribution.
Time frame: Up to 5 years
Duration of Response
Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier (1958).
Time frame: Up to 5 years
Time to Treatment Failure
Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they were removed from treatment. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier (1958). Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.
Time frame: Up to 5 years
Quality of Life, as Measure by the Mean Change in FACT-B TOI Score at Cycle 8
Quality of life (QOL) as measured by the mean change (from baseline) in FACT-B (TOI) Trial Outcome Index at Cycle 8 (24 weeks). FACT-B was scored according to the published scoring (\*) criteria with higher scores representing better QOL. The FACT-B TOI was the sum of the following FACT-B subscale/scale scores: physical (score range 0-28), functional (score range 0-28), and Breast Cancer Subscale (score range 0-40); range of the FACT-B TOI is 0-96 (the change scores have a possible range of -96 to 96). The mean change and 95% confidence interval are reported below. A one-sample t-test is used to compare the change from baseline to a value of 0. (\*)= Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality of life instrument. J Clin Oncol 1997;15:974-986.
Time frame: From baseline to end of Cycle 8; Up to 24 weeks
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Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, United States
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids, Iowa, United States
Medical Oncology and Hematology Associates - West Des Moines
Clive, Iowa, United States
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States
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